Hypomethylation of Cytosine 5-Methyltransferase in Human Neoplasms

Cytosine methylation is an epigenetic modification of DNA involved in control of gene expression. Neoplastic cells exhibit various alterations both in DNA methylation and activity of the enzyme responsible for this modification 5-methyl-transferase (5-MeTase). As there is little requirement for 5-methyltransferase expression in normal cells except during mitosis, we argued that the gene would be hypermethylated in normal cells. Southern analysis revealed almost complete methylation of the gene in genomic DNA from the peripheral blood leukocytes of healthy subjects and a primary fibroblast derived cell line. In contrast, in DNA from a range of tumour tissues and tumour derived cell lines, 5-MeTase exhibited marked hypomethylation. The results of this study indicate that dysregulation of the DNA methylating machinery, especially with respect to the methylation status of 5-MeTase, is a feature of a wide range of neoplasms.